Search

Objective: We aimed to confirm the effect of combined treatment with celecoxib and rebamipide would be more effective than celecoxib alone for prevention of upper gastrointestinal (GI) events., Methods: Patients with rheumatoid arthritis, osteoarthritis, and low back pain were enrolled in this study. Patients were randomized to two groups: a monotherapy group (100 mg celecoxib twice daily) and a combination therapy group (add on 100 mg of rebamipide three times a day). The GI mucosal injury was evaluated by endoscopic examination before treatment and at 3 months. The primary endpoint was to evaluate the preventive effect of the combination therapy group for GI events, endoscopic upper GI ulcers and intolerable GI symptoms, compared with the monotherapy group., Results: Seventy-five patients were enrolled. Sixty-five patients were analyzed (16 males, 49 females; mean age: 67 ± 13 years). The prevalence of upper GI events, five of endoscopic GI ulcers and one of intolerable GI symptoms, were 6/34 (17.6%) in the monotherapy group and 0/31 in the combination therapy group, p = 0.0252., Conclusions: The combination therapy group was more effective than the monotherapy group for prevention of upper GI events in this study. Rebamipide might be a candidate for an option to prevent COX-2 selective inhibitor-induced upper GI events.

Unlabelled: Expression of tenascin-C reappears in articular cartilage of persons with osteoarthritis (OA), while it is almost abolished in normal mature cartilage. Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, is upregulated in OA cartilage and is involved in the progression of OA, and stimulates tenascin-C expression in other types of cells. We investigated regulation of tenascin-C expression by TNF-alpha through nuclear factor-alphaB (NF-kappaB) in OA cartilage in vivo and in vitro., Methods: Human articular cartilages were obtained from patients with OA and immunofluorescence examination of tenascin-C and the activated RelA subunit was performed. Cultured chondrocytes isolated from human OA cartilage were treated with TNF-alpha and with SN50. Activation of RelA subunit of NF-kappaB was examined by immunolabeling. Changes in tenascin-C protein concentrations were determined by immunofluorescence of cells after monensin treatment and Western blot analysis of the cell lysates, and mRNA levels were analyzed by quantitative real-time polymerase chain reaction., Results: Increased intensity of tenascin-C staining was observed in the damaged cartilage compared with normal cartilage. Activated RelA staining in chondrocyte nuclei was prominent in tenascin-C-positive areas of OA cartilage. Treatment of cultured chondrocytes by TNF-alpha induced translocation of activated RelA to the nuclei, followed by upregulation of tenascin-C expression in both mRNA and protein. Treatment with SN50 inhibited increases of RelA and tenascin-C expression in chondrocytes., Conclusion: TNF-alpha stimulated tenascin-C expression through NF-kappaB signaling with RelA activation in cultured OA chondrocytes, suggesting involvement of tenascin-C in OA cartilage remodeling.

Osteoarthritis (MIM 165720), characterized by degeneration of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. Epidemiological and genetic studies have shown that osteoarthritis is a polygenic disease. Here, we report that the gene encoding growth differentiation factor 5 (GDF5) is associated with osteoarthritis in Asian populations. A SNP in the 5' UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 x 10(-13)) with hip osteoarthritis in two independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (P = 0.0021) and Han Chinese (P = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele showing reduced activity. Our findings implicate GDF5 as a susceptibility gene for osteoarthritis and suggest that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis.

Osteoarthritis is the most common form of human arthritis. We investigated the potential role of asporin, an extracellular matrix component expressed abundantly in the articular cartilage of individuals with osteoarthritis, in the pathogenesis of osteoarthritis. Here we report a significant association between a polymorphism in the aspartic acid (D) repeat of the gene encoding asporin (ASPN) and osteoarthritis. In two independent populations of individuals with knee osteoarthritis, the D14 allele of ASPN is over-represented relative to the common D13 allele, and its frequency increases with disease severity. The D14 allele is also over-represented in individuals with hip osteoarthritis. Asporin suppresses TGF-beta-mediated expression of the genes aggrecan (AGC1) and type II collagen (COL2A1) and reduced proteoglycan accumulation in an in vitro model of chondrogenesis. The effect on TGF-beta activity is allele-specific, with the D14 allele resulting in greater inhibition than other alleles. In vitro binding assays showed a direct interaction between asporin and TGF-beta. Taken together, these findings provide another functional link between extracellular matrix proteins, TGF-beta activity and disease, suggesting new therapeutic strategies for osteoarthritis.

This longitudinal study aimed to identify risk factors for the incidence and progression of radiographic knee osteoarthritis (OA). We examined the inhabitants of Miyagawa village aged ≥65 years every two years between 1997 and 2007. Anteroposterior radiographs of both knees were graded for OA using the Kellgren-Lawrence (K/L) grading system. Knee OA was defined as grade ≥2. We recorded the incidence of knee OA among participants in whom both knees changed from K/L grades 0 or 1 to ≥2 over a four-year follow-up period. We also recorded the progression of knee OA using this threshold among patients in whom one or both knees changed from K/L grades 2 or 3 to any higher grade over the follow-up period. Baseline data obtained from standard questionnaires, physical findings and X-rays included age, gender, body mass index (BMI), osteoporosis, Heberden's nodes, knee range of motion (ROM), knee pain and cigarette smoking. The rates of incidence and progression of knee OA among 360 participants (241 women, 119 men) who fulfilled the study criteria were 4.0 and 6.0% per year, respectively. Female gender (odds ratio [OR] 2.849, 95% confidence interval [CI] 1.170-6.944) and high BMI (OR 1.243, 95% CI 1.095-1.411) were significantly associated with the incidence of knee OA, and restricted knee ROM (OR 0.941, 95% CI 0.892-0.992) was significantly associated with knee OA progression. Patients with a low knee ROM relative to grade of radiographic knee OA require more careful follow-up than those with a higher ROM. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common disease that has a definite genetic component. Only a few OA susceptibility genes that have definite functional evidence and replication of association have been reported, however. Through a genome-wide association study and a replication using a total of ~4,800 Japanese subjects, we identified two single nucleotide polymorphisms (SNPs) (rs7775228 and rs10947262) associated with susceptibility to knee OA. The two SNPs were in a region containing HLA class II/III genes and their association reached genome-wide significance (combined P = 2.43 × 10-8 for rs7775228 and 6.73 × 10-8 for rs10947262). Our results suggest that immunologic mechanism is implicated in the etiology of OA. [ABSTRACT FROM AUTHOR]

Susceptibility to osteoarthritis, the most common human arthritis, is known to be influenced by genetic factors. Through a genome-wide association study using ∼100,000 SNPs, we have identified a previously unknown gene on chromosome 3p24.3, DVWA, which is associated with susceptibility to knee osteoarthritis. Expressed specifically in cartilage, DVWA encodes a 276-amino-acid protein with two regions corresponding to the von Willebrand factor type A domain (VWA domain). Several DVWA SNPs are significantly associated with knee osteoarthritis in two independent Japanese case-control cohorts. This association was replicated in a Japanese population cohort and a Han Chinese case-control cohort (combined P = 7.3 × 10−11). DVWA protein binds to β-tubulin, and the binding is influenced by two highly associated missense SNPs (rs11718863 and rs7639618) located in the VWA domain. The Tyr169-Cys260 isoform of DVWA, which is overrepresented in knee osteoarthritis, showed weaker interaction. Our findings reveal a new paradigm for study of osteoarthritis etiology and pathogenesis. [ABSTRACT FROM AUTHOR]

Tenascin-C (TN-C) is a hexameric glycoprotein component of extracellular matrix, and alternative RNA splicing creates two major TN-C size variants (the small and large variants). The large TN-C variants play key roles in many pathologic conditions in adults, including tumorigenesis, regeneration, and inflammation. This cross-sectional study compared levels of large TN-C variants in synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Synovial fluid samples were obtained from knees of 26 patients with advanced RA and 79 with advanced OA. Expression of TN-C splice variants was examined using Western blotting. The levels of large TN-C variants in synovial fluid were determined by an enzyme-linked immunosorbent assay. Synovium were analyzed for TN-C by immunohistochemistry. Immunoblotting showed the presence of large TN-C variants in synovial fluid from patients with RA and OA. However, levels of large TN-C variants were fourfold higher in RA samples compared with OA samples ( p < 0.01). Synovial fluid levels of TN-C in RA did not correlate with C-reactive protein levels. Immunohistochemistry of the synovium showed stronger reactivity in RA samples than in OA samples. These results indicate that local synthesis of TN-C is increased during rheumatic disease. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:563-568, 2007 [ABSTRACT FROM AUTHOR]

Heterotopic ossification after total knee arthroplasty is not well recognized. We found heterotopic ossification around the distal femur in 10 (5%) of 221 knees after primary total knee arthroplasty and evaluated clinical findings as well as risk factors. The duration of follow-up ranged from 1 to 5 years. Most patients with heterotopic ossification showed clinical findings that were suspected of being early infection after surgery such as continuing low-grade fever and erythematous, warm, and swollen knees, whereas blood examinations were normal. Heterotopic ossification developed by a mean period of 5 weeks, and the size increased for a mean period of 9 weeks. The maximum size of the ossification was <5 cm in 9 knees and >5 cm in 1 knee. After that, the size decreased without any treatment in all knees, and the ossification finally disappeared in 2 knees. Osteoarthrosis and the presence of postoperative effusion were the significant risk factors in the development of heterotopic ossification. Although it is difficult to draw valid conclusions from our small study, heterotopic ossification at the distal femur after total knee arthroplasty needed no treatment and was not progressive, nor did it affect the short-term outcome in this study. [ABSTRACT FROM AUTHOR]

We report a case of late small intestine perforation by an acetabular cup fixation screw after total hip arthroplasty (THA). A 79-year-old-woman underwent THA for hip osteoarthritis 13 years previously at another hospital. Although the acetabular cup fixation screw protruded into the pelvis, she had no symptoms. She later presented with peritonitis and was admitted to the hospital and prescribed antibiotic therapy. Computed tomography showed that the screw was adjacent to the intestine and was the likely cause of her peritonitis. After the peritonitis healed, she was referred to our hospital for surgical treatment of the screw. During laparotomy, we performed a resection of the intra-pelvic portion of the screw. The screw perforated the small intestine, so a small intestinal resection was also performed. The patient had an uneventful recovery. [ABSTRACT FROM AUTHOR]

Background: To investigate the prevalence and severity of radiographically detected hallux valgus (HV) as well as associated risk factors among Japanese residents of Miyagawa, a mountain village located in the center of Mie Prefecture. Methods: The height, weight and body mass index (BMI) of 403 participants (male n = 135, female n = 268) recruited from among the residents of Miyagawa Village, Japan aged ≥65 years were measured, and baseline data, including age, sex and medical history were obtained from interviews and questionnaires. Knee osteoarthritis (KOA) was determined from radiographs of the feet and knees, and osteoporosis was determined by measuring bone mineral density. Hallux valgus, defined as angulation of the big toe at the first metatarsophalangeal joint of >20°, was classified as: mild (20°-30°), moderate (30°-40°) or severe (>40°). Risk factors for HV were calculated using multivariate logistic regression analysis that included age, sex, obesity (BMI ≥25), KOA, osteoporosis, Heberden's nodes and low back pain as variables. Results: The overall prevalence of definite radiographic HV was 22.8 % (184/806), and mild, moderate and severe HV was found in 66.3, 27.2 and 6.5 % of the participants, respectively. Hallux valgus was found in at least one foot in 120 (29.8 %) of the participants and the prevalence significantly differed between females with and without HV and KOA (odds ratios: 2.54 and 1.71, respectively). Conclusions: The prevalence of definite radiographic HV was 29.8 %. Female sex and KOA were significantly associated with increased risk for radiographic HV. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the prevalence and characteristics of unilateral knee osteoarthritis (KOA), to investigate what percent of contralateral healthy knees in patients with unilateral KOA progress to KOA, and to investigate whether knee fractures influence unilateral KOA. Methods: Studies were performed every two years from 1997 to 2009 in Miyagawa village, for a total of seven studies. A total of 1239 village inhabitants aged ≥65 years participated in these studies at least once. KOA was defined as a Kellgren-Lawrence (K/L) grade ≥2. Based on the knee X-ray at the first examination, participants were divided into three groups: no KOA (N group), unilateral KOA (U group), and bilateral KOA (B group). The U group was divided into two subgroups: K/L grade II-I combination (II-I group), and the U group without the II-I combination (G>2 group). To investigate whether knee fractures influence unilateral KOA, the fracture history was considered. Results: The percentages of participants classified into the N, B, and U groups (II-I and G>2 group) were 68.4, 21.6, and 10.0 % (7.8 and 2.1 %), respectively. Most of the U group had the II-I combination (78.7 %). The percentages of knee fractures in the N, B, II-I, and G>2 groups were 3.3, 5.3, 6.3, and 38.5 %, respectively. Overall, 49.2 % of the U group proceeded to bilateral KOA over an average of 5.3 years. Conclusions: The prevalences of definite radiographic bilateral and unilateral KOA were 21.6 and 10.0 %, respectively. Overall, 49.2 % of the participants with unilateral KOA developed KOA in the contralateral knee over an average of 5.3 years. If bilateral KOA advanced simultaneously, the II-I group was considered to represent the midpoint of progression to bilateral KOA. Bilateral KOA advanced simultaneously except in cases with a history of knee trauma, such as fractures. [ABSTRACT FROM AUTHOR]

Background: Tenascin-C (TN-C) is expressed in the cartilage of osteoarthritis (OA). We examined whether TN-C was involved in cartilage repair of the diseased joints. Human articular cartilage samples were obtained from patients with OA and those with normal joints. Methods: Immunohistochemistry testing of TN-C, chondroitin sulfate (CS), and proliferating cell nuclear antigen (PCNA) was performed. Chondrocytes were isolated from human cartilage and cultured. After treatment with TN-C, chondrocyte proliferation s was analyzed by bromodeoxyuridine (BrdU) incorporation assay using an enzyme-linked immunosorbent assay kit. Glycosaminoglycan content was determined by dimethylmethylene blue (DMMB) assay. The mRNA expression of aggrecan was also analyzed, by quantitative real-time polymerase chain reaction (PCR). Results: In osteoarthritic cartilage, increased TN-C staining was observed with the degeneration of articular cartilage in comparison with normal cartilage. TN-C staining was shown in the cartilage surface overlying CS-positive areas. In addition, the expression of PCNA in the positive areas for TN-C was significantly higher than that in the negative areas. Treatment of human articular chondrocytes with 10 μg/ml TN-C accelerated chondrocyte proliferation, increased the proteoglycan amount in culture, and increased the expression of aggrecan mRNA. Conclusions: Our findings indicate that the distribution of TN-C is related to CS production and chondrocyte proliferation in osteoarthritic cartilage and that TN-C has effects on DNA synthesis, proteoglycan content, and aggrecan mRNA expression in vitro. TN-C may be responsible for repair in human osteoarthritic cartilage. [ABSTRACT FROM AUTHOR]

Abstract: Osteogenesis imperfecta (OI) is a rare congenital disorder of type І collagen production that results in brittle bones and affects body systems containing collagen. The increasing life span of patients with OI has recently revealed a high incidence of osteoarthritis of the knee. A 53 year-old man with OI presented with bilateral knee pain. He had severe deformities of the proximal part of the femur with subsegment post-traumatic osteoarthritis of both sides of the knees. However, the frequency of fracture gradually decreased and he had not experienced a fracture for 17 years. His bone mineral density was extremely low for his age. He underwent cemented total knee arthroplasty (TKA) on the left knee. One year later, the patient had relief of pain and he could walk without assistance. To our knowledge, only three knee replacements in two patients with OI have been reported, so this case is extremely rare. Although whether a patient with OI is a suitable candidate for knee replacement, it was a useful treatment for osteoarthritis in this case. [Copyright &y& Elsevier]